In the PROGRAM OVERVIEW section of our parent R24 application, we argued that careful study of SESatypical communities and individuals could yield key insights into what is arguably the most powerful, enduring and yet enigmatic association in the field of mind-body health and, more generally, the field of population health science. Why do some children thrive and flourish despite rearing experiences in blighted, disadvantaged socioeconomic conditions? Why do others founder[unreadable]developmentally, psychologically, physically[unreadable]in circumstances of wealth, abundance and unlimited resource availability? More generally, why do most children follow developmental paths staunchly typical of the social class into which they were born, while others show striking signs of atypical resilience or vulnerability? We argued that a precondition to answering such questions would be fundamentally new knowledge of the neurobiological and genetic substrates underlying SES-atypicality[unreadable]that is, how early social environmental exposures and epigenetic regulation of gene expression work together to influence a child's susceptibility v. resilience to compromised and disadvantaged social circumstances. Finally, we argued that informative studies of the biological processes underlying SES vulnerability and resilience would require genuinely population-level analysis and the capacity for strategically sampling communities of children with known socioeconomic and developmental attributes. Only population-based data will allow unbiased ascertainment of gene-environment interplay within targeted SES-typical and -atypical groups. This first of five projects advanced within an R24 application on Social Disparities in Epigenetic Regulation of Neurodevelopment thus proposes to explore the feasibility of joining social epidemiology to cutting-edge molecular genetics through the exploitation of a truly unique and largely untapped scientific resource: a set of linkable, whole-population databases from the Canadian province of British Columbia: databases that collectively access genetic, biomedical, developmental, educational, and socioeconomic information on an entire societal jurisdiction of children. The size, breadth and depth of these data[unreadable]from a province with an established and universal health care system[unreadable]proffer an unprecedented opportunity for careful, precisely crafted studies of the early biological foundations of health disparities. Our proposed Project 1[unreadable]on Epigenetic Modifications and Social Disparities in Neurodevelopmental Vulnerability[unreadable]comprises two sub-studies, with five specific aims. The first sub-study (Sub-Study A) seeks to confirm and extend a striking and potentially important finding from our prior, R21 pilot research: that prepubertal children from low SES families, relative to children from high SES families, show systematic eventrelated potential (ERP) deficits in lateral prefrontal cortical processing of novel stimuli. Such differences in cognitive neurodevelopment appearing within the first decade of life, if confirmed in subsequent, broader study samples, could constitute one of the biological bases of lifelong, SES-related differences in academic achievement, job performance and learning. It is indeed likely that neurobiological disparities of this kind are related to the tenacity with which social class membership generally persists[unreadable]unchanged[unreadable]over a lifetime of individual experience. The second sub-study (Sub-Study B), addresses the biological roots of SES-atypicality at an even more fundamental, molecular level and proposes to explore the practicality and scientific promise of using population-level epidemiologic data to examine differences in DNA methylation among children from varying socioeconomic strata. Sub-Study B[unreadable]by further extending epidemiologic linkages among the BC data sets and examining patterns of epigenetic modification within targeted groups of SES-atypical children[unreadable]will generate provisional but groundbreaking observations on epigenomic dissimilarities among children from distinctive social backgrounds. To our knowledge, Sub-Studies A and B would be the first to detect and codify experience-dependent, neurobiological and epigenetic changes within epidemiologic samples of young, socioeconomically diverse children.